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Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis
Uncertainty exists as to whether similar or different mechanisms contribute to the pathogenesis of different subtypes of multiple sclerosis (MS). Detailed analysis of naive T cell homeostasis shows that patients with relapsing-remitting MS (RRMS) and with primary progressive MS (PPMS) have early-ons...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Hindawi Publishing Corporation
2011
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197186/ https://www.ncbi.nlm.nih.gov/pubmed/22096637 http://dx.doi.org/10.1155/2011/461304 |
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author | Haegert, David G. |
author_facet | Haegert, David G. |
author_sort | Haegert, David G. |
collection | PubMed |
description | Uncertainty exists as to whether similar or different mechanisms contribute to the pathogenesis of different subtypes of multiple sclerosis (MS). Detailed analysis of naive T cell homeostasis shows that patients with relapsing-remitting MS (RRMS) and with primary progressive MS (PPMS) have early-onset thymic involution that causes reduced thymic output. The reduced thymic output leads to secondary peripheral homeostatic alterations in naïve CD4 T-cells, which closely mimic T-cell alterations observed in an experimental animal model of diabetes mellitus. Homeostatic T-cell receptor (TCR) signalling and proliferation of naïve T cells are induced by self-peptides. Consequently, the findings of increased TCR signalling of naïve CD4 T-cells, without increased proliferation, in PPMS, and the increased homeostatic proliferation of naïve CD4 T-cells in RRMS favour the development of autoimmunity. Thus, it seems highly likely that peripheral T-cell alterations secondary to a thymic abnormality contribute to the pathogenesis of both MS subtypes. |
format | Online Article Text |
id | pubmed-3197186 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-31971862011-11-17 Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis Haegert, David G. Mult Scler Int Review Article Uncertainty exists as to whether similar or different mechanisms contribute to the pathogenesis of different subtypes of multiple sclerosis (MS). Detailed analysis of naive T cell homeostasis shows that patients with relapsing-remitting MS (RRMS) and with primary progressive MS (PPMS) have early-onset thymic involution that causes reduced thymic output. The reduced thymic output leads to secondary peripheral homeostatic alterations in naïve CD4 T-cells, which closely mimic T-cell alterations observed in an experimental animal model of diabetes mellitus. Homeostatic T-cell receptor (TCR) signalling and proliferation of naïve T cells are induced by self-peptides. Consequently, the findings of increased TCR signalling of naïve CD4 T-cells, without increased proliferation, in PPMS, and the increased homeostatic proliferation of naïve CD4 T-cells in RRMS favour the development of autoimmunity. Thus, it seems highly likely that peripheral T-cell alterations secondary to a thymic abnormality contribute to the pathogenesis of both MS subtypes. Hindawi Publishing Corporation 2011 2011-09-15 /pmc/articles/PMC3197186/ /pubmed/22096637 http://dx.doi.org/10.1155/2011/461304 Text en Copyright © 2011 David G. Haegert. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Haegert, David G. Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis |
title | Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis |
title_full | Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis |
title_fullStr | Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis |
title_full_unstemmed | Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis |
title_short | Multiple Sclerosis: A Disorder of Altered T-Cell Homeostasis |
title_sort | multiple sclerosis: a disorder of altered t-cell homeostasis |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3197186/ https://www.ncbi.nlm.nih.gov/pubmed/22096637 http://dx.doi.org/10.1155/2011/461304 |
work_keys_str_mv | AT haegertdavidg multiplesclerosisadisorderofalteredtcellhomeostasis |